Mycophenolate mofetil prevents salt-sensitive hypertension resulting from nitric oxide synthesis inhibition

被引:154
作者
Quiroz, Y
Pons, H
Gordon, KL
Rincón, J
Chávez, M
Parra, G
Herrera-Acosta, J
Gómez-Garre, D
Largo, R
Egido, J
Johnson, RJ
Rodríguez-Iturbe, B
机构
[1] Univ Zulia, Univ Hosp, Renal Serv, Maracaibo 4001A, Venezuela
[2] Univ Zulia, Univ Hosp, Dept Immunobiol INBIOMED, Maracaibo 4001A, Venezuela
[3] Inst Nacl Cardiol, Dept Nephrol, Mexico City 4080, DF, Mexico
[4] Univ Autonoma Madrid, Fdn Jimenez Diaz, Lab Nefrol, Madrid 28040, Spain
关键词
lymphocytes; nitric oxide inhibition; angiotensin II-positive cells;
D O I
10.1152/ajprenal.2001.281.1.F38
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Recent studies have suggested that subtle microvascular and tubulointerstitial injury in the kidney can cause salt-sensitive hypertension. To test this hypothesis, we determined whether the mild renal disease induced by transient blockade of nitric oxide (NO) synthesis would result in salt-sensitive hypertension and whether prevention of the renal injury by coadministration of the immunosuppressive agent mycophenolate mofetil (MMF) would block the development of salt sensitivity. N-omega-nitro-L-arginine-methyl ester (L-NAME; 70 mg/100 ml in the drinking water) was administered for 3 wk to rats with or without MMF (30 mg.kg(-1).day(-1) by gastric gavage), followed by a 1-wk "washout" period in which the MMF was continued, which was followed in turn by placement on a high-salt (4% NaCl) diet for an additional 4 wk. Renal histology was examined at 3 and 8 wk, and blood pressure was measured serially. L-NAME treatment resulted in acute hypertension and the development of mild renal injury. During the washout period, blood pressure returned to normal, only to return to the hypertensive range on exposure of the animals to a high-salt diet. MMF treatment prevented the development of hypertension in response to a high-salt diet. This correlated with the ability of MMF to inhibit specific aspects of the renal injury, including the development of segmental glomerulosclerosis, the infiltration of T cells and ANG II-positive cells, and the thickening of afferent arterioles.
引用
收藏
页码:F38 / F47
页数:10
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